Synthesis and antimicrobial activities of $N^{6}-hydroxyagelasine$ analogs and revision of the structure of ageloximes

(+)-N6-Hydroxyagelasine D, the enantiomer of the proposed structure of (−)-ageloxime D, as well as N6-hydroxyagelasine analogs were synthesized by selective N-7 alkylation of N6-[tert-butyl(dimethyl)silyloxy]-9-methyl-9H-purin-6-amine in order to install the terpenoid side chain, followed by fluoride mediated removal of the TBDMS-protecting group. N6-Hydroxyagelasine D and the analog carrying a geranylgeranyl side chain displayed profound antimicrobial activities against several pathogenic bacteria and protozoa and inhibited bacterial biofilm formation. However these compounds were also toxic towards mammalian fibroblast cells (MRC-5). The spectral data of N6-hydroxyagelasine D did not match those reported for ageloxime D before. Hence, a revised structure of ageloxime D was proposed. Basic hydrolysis of agelasine D gave (+)-N-[4-amino-6-(methylamino)pyrimidin-5-yl]-N-copalylformamide, a compound with spectral data in full agreement with those reported for (−)-ageloxime D.

Publication year:2019

Keywords:A1 Journal article

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BOF-publication weight:1

CSS-citation score:1

Authors:International

Authors from:Higher Education

Accessibility:Open